NF-kappaB2 (p100) limits TNF-alpha-induced osteoclastogenesis

J Clin Invest. 2009 Oct;119(10):2879-81. doi: 10.1172/JCI40629. Epub 2009 Sep 21.


Bone undergoes a continuous cycle of renewal, and osteoclasts--the cells responsible for bone resorption--play a pivotal role in bone homeostasis. This resorption is largely mediated by inflammatory cytokines such as TNF-alpha. In this issue of the JCI, Yao et al. demonstrate that the NF-kappaB precursor protein NF-kappaB2 (p100) acts as a negative regulator of osteoclastogenesis (see the related article beginning on page 3024). TNF-alpha induced a sustained accumulation of p100 in osteoclast precursors, and TNF-alpha-induced osteoclast formation was markedly increased in Nfkb2-/- mice. They also found that TNF receptor-associated factor 3 (TRAF3) is involved in the posttranslational regulation of p100 expression. These results suggest that blockade of the processing of p100 is a novel strategy to treat TNF-alpha-related bone diseases such as RA.

Publication types

  • Comment

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Mice
  • Mice, Knockout
  • NF-kappa B p52 Subunit / genetics
  • NF-kappa B p52 Subunit / metabolism*
  • Osteoclasts / cytology
  • Osteoclasts / physiology*
  • Signal Transduction / physiology
  • TNF Receptor-Associated Factor 3 / genetics
  • TNF Receptor-Associated Factor 3 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*


  • NF-kappa B p52 Subunit
  • TNF Receptor-Associated Factor 3
  • Tumor Necrosis Factor-alpha